Abstract
The purpose of this study was to investigate local and network‐related changes of limbic grey matter in early Parkinson's disease (PD) and their inter‐relation with non‐motor symptom severity. We applied voxel‐based morphometric methods in 538 T1 MRI images retrieved from the Parkinson's Progression Markers Initiative website. Grey matter densities and cross‐sectional estimates of age‐related grey matter change were compared between subjects with early PD (n = 366) and age‐matched healthy controls (n = 172) within a regression model, and associations of grey matter density with symptoms were investigated. Structural brain networks were obtained using covariance analysis seeded in regions showing grey matter abnormalities in PD subject group. Patients displayed focally reduced grey matter density in the right amygdala, which was present from the earliest stages of the disease without further advance in mild‐moderate disease stages. Right amygdala grey matter density showed negative correlation with autonomic dysfunction and positive with cognitive performance in patients, but no significant interrelations were found with anxiety scores. Patients with PD also demonstrated right amygdala structural disconnection with less structural connectivity of the right amygdala with the cerebellum and thalamus but increased covariance with bilateral temporal cortices compared with controls. Age‐related grey matter change was also increased in PD preferentially in the limbic system. In conclusion, detailed brain morphometry in a large group of early PD highlights predominant limbic grey matter deficits with stronger age associations compared with controls and associated altered structural connectivity pattern. This provides in vivo evidence for early limbic grey matter pathology and structural network changes that may reflect extranigral disease spread in PD. Hum Brain Mapp 38:3566–3578, 2017. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.
Highlights
Using FMRIB software library (FSL)-voxel-based morphometry (VBM), we found few deficits in grey matter density in Parkinson’s disease (PD) compared to healthy controls (PD < healthy controls) most notably in the right amygdala region (Fig. 1 and Table II)
There were no regions with increased grey matter density in PD compared with healthy controls using both family-wise error (FWE) threshold correction method and uncorrected methods
To the best of our knowledge, we report the first investigation of a link between autonomic dysfunction and amygdala grey matter reduction in Parkinson’s
Summary
Received for publication 15 June 2016; Revised 10 March 2017; Accepted 28 March 2017. Published online 00 Month 2017 in Wiley Online Library (wileyonlinelibrary.com). Parkinson’s disease (PD) is the second-most common neurodegenerative disorder, affecting up to 2% of individuals aged 65 years and older [Hanganu et al, 2014]. The hallmark motor symptoms (bradykinesia, rigor and tremor) are thought to share the same fundamental aetiology related to dopaminergic cell death in the substantia nigra pars compacta and subsequent reduction of striatal dopaminergic innervation [Brown, 2003]. The pathophysiology of nonmotor dysfunction is less well understood, and may reflect
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